Improvement in touch sensation after stroke is associated with resting functional connectivity changes

I don't give a shit what your conclusions are, you should not have any stroke research funded without coming up with a translational plan to put your results into a stroke protocol. Worthless crap.
http://journal.frontiersin.org/article/10.3389/fneur.2015.00165/full?utm_source=newsletter&utm_medium=email&utm_campaign=Neurology-w35-2015

Louise C. Bannister^1,2,3, Sheila G. Crewther², Maria Gavrilescu^1,4 and Leeanne M. Carey^1,3,5*

• ¹Neurorehabilitation and Recovery, Stroke Division, Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia
• ²School of Psychology and Public Health, College of Science, Health and Engineering, La Trobe University, Melbourne, VIC, Australia
• ³Occupational Therapy, School of Allied Health, College of Science, Health and Engineering, La Trobe University, Melbourne, VIC, Australia
• ⁴Defence Science and Technology Organisation, Melbourne, VIC, Australia
• ⁵Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, Australia

Background: Distributed brain networks are known to be involved in facilitating behavioral improvement after stroke, yet few, if any, studies have investigated the relationship between improved touch sensation after stroke and changes in functional brain connectivity.

Objective: We aimed to identify how recovery of somatosensory function in the first 6 months after stroke was associated with functional network changes as measured using resting-state connectivity analysis of functional magnetic resonance imaging (fMRI) data.

Methods: Ten stroke survivors underwent clinical testing and resting-state fMRI scans at 1 and 6 months post-stroke. Ten age-matched healthy participants were included as controls.

Results: Patients demonstrated a wide range of severity of touch impairment 1 month post-stroke, followed by variable improvement over time. In the stroke group, significantly stronger interhemispheric functional correlations between regions of the somatosensory system, and with visual and frontal areas, were found at 6 months than at 1 month post-stroke. Clinical improvement in touch discrimination was associated with stronger correlations at 6 months between contralesional secondary somatosensory cortex (SII) and inferior parietal cortex and middle temporal gyrus, and between contralesional thalamus and cerebellum.

Conclusion: The strength of connectivity between somatosensory regions and distributed brain networks, including vision and attention networks, may change over time in stroke survivors with impaired touch discrimination. Connectivity changes from contralesional SII and contralesional thalamus are associated with improved touch sensation at 6 months post-stroke. These functional connectivity changes could represent future targets for therapy.

Introduction

Somatosensory impairment is common after stroke, occurring in 50–80% of stroke survivors (1, 2). However, investigations of the neural correlates of clinical somatosensory improvement after stroke are scarce (3). In particular, knowledge of how brain networks are interrupted is limited, but is critical to better understand the nature of the clinical deficit and post-stroke recovery (4).

Stroke impacts not only the focal lesion site but also on remote brain regions (5, 6). Lesions have important remote effects on the function of connected neural networks that are structurally intact, i.e., physiological changes in distant but functionally related brain areas (4, 7, 8). These remote effects contribute significantly to the observed behavioral deficits and recovery potential (4, 8). Further, changes in brain networks (across both hemispheres and function-specific networks) have been shown to be important in recovery of motor and attention functions (4, 6). A significant challenge is to identify the brain networks and processes that mediate functional improvement so that rehabilitation strategies can be aimed at the appropriate targets (9).

Only a few studies have investigated changes in the brain over time in association with somatosensory recovery (3, 10–13). These studies have primarily involved identification of brain regions associated with task-related brain activation. A few studies have reported that somatosensory recovery is associated with patterns of activation in primary somatosensory (SI) cortex that resembles those seen in healthy controls. For example, return of ipsilesional SI activation has been shown to be associated with improved somatosensory perception (10–12). Staines et al. (12) found that enhanced primary somatosensory cortex activation using functional MRI in the stroke-affected hemisphere occurred in conjunction with improved touch detection in four patients with thalamocortical strokes. Likewise, Wikström et al. (10) reported that increased amplitude of early somatosensory evoked fields in the ipsilesional SI in response to median nerve simulation was associated with recovery of two-point discrimination (the ability to discern that two nearby objects touching the skin are truly two distinct points, not one) in stroke patients.

While relative “normalization” of brain activity in primary and secondary (SII) somatosensory regions in both hemispheres seems to underlie good clinical recovery, patients with more severe impairments have been shown to recruit attention and multisensory brain regions to a greater degree than that seen in healthy controls, in order to accomplish successful task performance (3, 11, 14–17). In an early positron emission tomography (PET) study of five patients after subcortical stroke, Weder et al. (14) reported activation across bilateral sensorimotor cortex and distributed regions, such as premotor cortex and cerebellum, with worse performance on a tactile shape discrimination task found to correlate with bilateral sensorimotor cortex activation. Tecchio et al. (16) used magnetoencephalography (MEG) to study 18 patients at the acute (5 days) and post-acute (6 months) stages after stroke. They reported that excessive interhemispheric asymmetry correlated with a greater degree of clinical improvement over time in those patients who showed partial recovery. Taskin et al. (15) reported reduced activation of ipsilesional SI with preserved responsiveness of SII in six patients who had suffered thalamic strokes. More recently, in 19 patients, a study into the relationship between touch impairment and interruption to cortical and subcortical somatosensory areas revealed that the neural correlates of touch impairment in patients with interruption to subcortical somatosensory areas (e.g., thalamus), involved a distributed network of ipsilesional SI and SII, contralesional thalamus, and attention-related frontal and occipital regions (3).

Use of task-based brain activation paradigms can be challenging for stroke patients who may have difficulty performing a given task, and inability to perform the task may impact on the validity of the results (18). Resting-state functional connectivity analysis of functional magnetic resonance imaging (fMRI) data has more recently been employed as a way of assessing activity in the brain over time and across different networks of the brain (19, 20). Resting-state functional connectivity reveals intrinsic, spontaneous networks that elucidate the functional architecture of the human brain at rest (task-independent). Functional connectivity is defined as the statistical association (or temporal correlation) among two or more anatomically distinct regions (21). Data are analyzed for coherence across the whole brain and/or in relation to particular regions of interest (ROIs). Evidence suggests that this measure is indicative of behaviorally relevant brain networks without requiring task performance (22). Consistent resting-state networks, with sharp transitions in correlation patterns, are reliably detected in individual and group data (23, 24).

In stroke patients, use of this technique has revealed disruption of functional connectivity of brain networks, even within structurally intact brain regions (6, 25, 26). Changes in functional connectivity have been described in motor recovery under resting-state and task-related conditions (27). Further, changes in functional connectivity over time have been found to occur in conjunction with behavioral change, both in healthy individuals (22) and in stroke patients (7, 25). For example, He and colleagues (25) reported that in patients with spatial neglect, dorsal attention network connectivity was disrupted early after stroke, but appeared to have improved to similar levels as controls by 9 months post-stroke, in conjunction with behavioral improvement. This supports the interpretation that different networks or areas of the brain may dynamically change and assume different roles to allow behavior to occur.

The aim of the current study was to identify longitudinal changes in functional connections of the somatosensory network in stroke patients with somatosensory impairment, and to establish if and how these correlations are associated with improvement in touch discrimination.

The importance of interhemispheric functional connectivity in behavioral performance and recovery has been highlighted from studies using resting-state fMRI (rsfMRI) with animal and human stroke populations (7, 25, 28). The most consistent finding is of changes in interhemispheric functional connectivity between homotopic areas, such as ipsilesional and contralesional primary motor cortex (7). Longitudinal changes have also been reported. Decreased interhemispheric functional connectivity of the ipsilesional sensorimotor cortex has been reported early after stroke, with return to more normal levels during the recovery process (7, 29, 30). These findings are not surprising given that interhemispheric connections are implicated in sensory (31) and cognitive processing (32) and in models of motor and somatosensory recovery (33–37). Thus, changes in interhemispheric functional connectivity in stroke patients and associations between these changes and behavioral improvement are expected. We hypothesized that over time, stroke patients would exhibit return to a more “typical” pattern of interhemispheric functional connectivity between homologous cortical somatosensory regions, and that stronger interhemispheric resting-state functional correlations between homologous SI and SII regions at 6 months than at 1 month post-stroke would be associated with clinical improvement.

Increased connectivity with distributed networks has also been reported in recovery after stroke. First, the visual system drives human attention and planning (38, 39), and a rich history of evidence for cross-modal plasticity between the visual and somatosensory systems exists (40). Recruitment of visual areas has been reported in previous studies of motor recovery after stroke (30, 41) as well as in patients with somatosensory impairment after stroke (3). Second, greater recruitment of attention systems is known to be necessary (42) to compensate for the impairment of function-specific brain areas due to aging or injury (43, 44). In stroke patients, increased attention has been shown to be required to accomplish previously simple tasks, such as walking, and attention skills have been shown to predict outcome after stroke (42, 45). Increased activation of frontoparietal attention areas, such as inferior parietal cortex (IPC), has been reported to occur in recovering stroke patients with motor problems (46–48). Thus, greater functional connections with frontoparietal attention networks could be expected in stroke patients with somatosensory impairment. As such, we predicted that stronger thalamocortical and cortico-cortical functional correlations with frontoparietal visual attention networks at 6 months post-stroke would be associated with clinical improvement.

More at link, not that it will help any survivor.